This is an application for a supplement comprised of two research projects and a supplement to Administrative Core of this ongoing program project now in its 7th year of funding. One project (I-E) is concerned with the chemical, physiological and morphological definition of a new glycoprotein, fibronectin, found in the lung basement membrane. The second proposal is a supplement to the 08 year funding of Project II-A concerned with the role of the cellular and structural effects of lung parenchymal injury on the metabolic fate of vasoactive substances in the lung. The application includes a request for continuation of funding of II-A to the 9th and 10th year. The overall objective of this program project has been to define for the lung the chemical, cellular and physiological characteristics which predispose the lung to injury in vivo. A major portion of the investigation concerns the definition of the content, composition and in vivo functions of lung elastin, collagen and glycosaminoglycans. Studies of lung tissue injury are focussed on proteolysis, inhibition of proteolysis, degradation of lung connective tissue and its resynthesis. Parallel studies involve the physical-chemical significance of connective tissue structure and its geometric configuration in lung as determinants of the mechanical characteristics of lung parenchyma at the alveolar level, as well as overall lung pressure volume characteristics. A major portion of the overall program project is involved in the investigation of the role of cellular and structural effects of lung parenchymal injury on the metabolic fate of vasoactive substances in the lung including kinins, which are transported through the mixed venous circulation to the lung or elaborated in lung tissue. Important components of study in each aspect of the program project is the use of cell culture for definition of chemical and degradative processes for specific lung cells and correlations of light microscopy and ultrastructural morphology with studies of chemical synthesis, proteolysis, and the production experimentally of pathogenic lesions of the lung.